EP0440147A3 - Preparation and use of a human antibody gene bank (human antibody libraries) - Google Patents

Preparation and use of a human antibody gene bank (human antibody libraries) Download PDF

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Publication number
EP0440147A3
EP0440147A3 EP19910101095 EP91101095A EP0440147A3 EP 0440147 A3 EP0440147 A3 EP 0440147A3 EP 19910101095 EP19910101095 EP 19910101095 EP 91101095 A EP91101095 A EP 91101095A EP 0440147 A3 EP0440147 A3 EP 0440147A3
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EP
European Patent Office
Prior art keywords
human antibody
preparation
human
cdna
gene bank
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP19910101095
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German (de)
Other versions
EP0440147B1 (en
EP0440147A2 (en
EP0440147B2 (en
Inventor
Melvyn Dr. Little
Frank Berthold Breitling
Thomas Dr. Seehaus
Stefan Duebel
Iris Klewinghaus
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Siemens Healthcare Diagnostics Products GmbH
Original Assignee
Behringwerke AG
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Publication date
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=25889602&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP0440147(A3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from DE4002898A external-priority patent/DE4002898A1/en
Priority claimed from DE4003881A external-priority patent/DE4003881A1/en
Application filed by Behringwerke AG filed Critical Behringwerke AG
Priority to EP04008412A priority Critical patent/EP1566442B1/en
Publication of EP0440147A2 publication Critical patent/EP0440147A2/en
Publication of EP0440147A3 publication Critical patent/EP0440147A3/en
Publication of EP0440147B1 publication Critical patent/EP0440147B1/en
Anticipated expiration legal-status Critical
Application granted granted Critical
Publication of EP0440147B2 publication Critical patent/EP0440147B2/en
Expired - Lifetime legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034Isolating an individual clone by screening libraries
    • C12N15/1093General methods of preparing gene libraries, not provided for in other subgroups
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/44Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/06Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/65Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression using markers
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/70Vectors or expression systems specially adapted for E. coli
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/88Lyases (4.)
    • CCHEMISTRY; METALLURGY
    • C40COMBINATORIAL TECHNOLOGY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B30/00Methods of screening libraries
    • C40B30/04Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531Production of immunochemical test materials
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6845Methods of identifying protein-protein interactions in protein mixtures
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854Immunoglobulins
    • G01N33/6857Antibody fragments
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/01Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Plant Pathology (AREA)
  • Food Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

The gene library of human antibodies is taken from a mixture of human B-lymphocytes. Their mRNA are converted into cDNA using oligo-dT primers. The cDNA specific to antibodies are amplified by PCR with suitable oligonucleotide primer sequences. Using an expression of the antibody-specific cDNA in a bacterial expression vector, e.g. in E. coli, a human antibody library is produced with a wide range for screening with selected antigens in vitro.
EP91101095.7A 1990-02-01 1991-01-28 Preparation and use of a human antibody gene bank (human antibody libraries) Expired - Lifetime EP0440147B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP04008412A EP1566442B1 (en) 1990-02-01 1991-01-28 Preparation and use of a human antibody gene bank (human antibody libraries)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE4002898A DE4002898A1 (en) 1990-02-01 1990-02-01 Human antibody library
DE4002898 1990-02-01
DE4003881A DE4003881A1 (en) 1990-02-09 1990-02-09 Human antibody library
DE4003881 1990-02-09

Related Child Applications (3)

Application Number Title Priority Date Filing Date
EP04008412A Division EP1566442B1 (en) 1990-02-01 1991-01-28 Preparation and use of a human antibody gene bank (human antibody libraries)
EP04008412A Division-Into EP1566442B1 (en) 1990-02-01 1991-01-28 Preparation and use of a human antibody gene bank (human antibody libraries)
EP04008412.1 Division-Into 2004-04-07

Publications (4)

Publication Number Publication Date
EP0440147A2 EP0440147A2 (en) 1991-08-07
EP0440147A3 true EP0440147A3 (en) 1992-07-08
EP0440147B1 EP0440147B1 (en) 2004-09-22
EP0440147B2 EP0440147B2 (en) 2014-05-14

Family

ID=25889602

Family Applications (2)

Application Number Title Priority Date Filing Date
EP91101095.7A Expired - Lifetime EP0440147B2 (en) 1990-02-01 1991-01-28 Preparation and use of a human antibody gene bank (human antibody libraries)
EP04008412A Expired - Lifetime EP1566442B1 (en) 1990-02-01 1991-01-28 Preparation and use of a human antibody gene bank (human antibody libraries)

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP04008412A Expired - Lifetime EP1566442B1 (en) 1990-02-01 1991-01-28 Preparation and use of a human antibody gene bank (human antibody libraries)

Country Status (12)

Country Link
US (1) US6319690B1 (en)
EP (2) EP0440147B2 (en)
JP (1) JP3514778B2 (en)
KR (1) KR100186823B1 (en)
AT (2) ATE449853T1 (en)
AU (1) AU633682B2 (en)
CA (1) CA2035381C (en)
DE (2) DE59109273D1 (en)
DK (1) DK0440147T3 (en)
ES (2) ES2225816T5 (en)
IE (1) IE910335A1 (en)
PT (1) PT96625B (en)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
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DK0440147T3 (en) 1990-02-01 2005-01-17 Dade Behring Marburg Gmbh Preparation and use of human antibody gene banks ("human antibody libraries")
IE922287A1 (en) * 1991-07-15 1993-01-27 Wellcome Found Production of antibodies
DE4142077A1 (en) * 1991-12-19 1993-06-24 Boehringer Mannheim Gmbh METHOD FOR EXPRESSING RECOMBINANT ANTIKOERPERS
AU1736495A (en) * 1994-01-31 1995-08-15 Trustees Of Boston University Polyclonal antibody libraries
DE19728697C1 (en) * 1997-07-04 1999-03-25 Deutsches Krebsforsch Human antibody against a fusion (poly) peptide or protein which contains at least six histidines
AU9148498A (en) * 1997-09-19 1999-04-12 Medleys Laboratories Inc. Method and kit for early diagnosis of autoimmunity and lymphoma in central nervous system
US7270969B2 (en) * 1999-05-05 2007-09-18 Phylogica Limited Methods of constructing and screening diverse expression libraries
US6994982B1 (en) * 1999-05-05 2006-02-07 Phylogica Limited Isolating biological modulators from biodiverse gene fragment libraries
US7803765B2 (en) * 1999-05-05 2010-09-28 Phylogica Limited Methods of constructing biodiverse gene fragment libraries and biological modulators isolated therefrom
EP2199393B1 (en) * 2000-04-17 2012-10-31 Dyax Corp. Methods of constructing display libraries of genetic packages for members of a diverse family of peptides
US8288322B2 (en) 2000-04-17 2012-10-16 Dyax Corp. Methods of constructing libraries comprising displayed and/or expressed members of a diverse family of peptides, polypeptides or proteins and the novel libraries
JP4860098B2 (en) 2000-12-18 2012-01-25 ダイアックス、コープ Library focused on genetic packaging
WO2003035842A2 (en) * 2001-10-24 2003-05-01 Dyax Corporation Hybridization control of sequence variation
US20040067532A1 (en) 2002-08-12 2004-04-08 Genetastix Corporation High throughput generation and affinity maturation of humanized antibody
CA2553692C (en) 2004-01-20 2014-10-07 Kalobios, Inc. Antibody specificity transfer using minimal essential binding determinants
US20050282233A1 (en) * 2004-03-05 2005-12-22 Ludwig Institute For Cancer Research Multivalent antibody materials and methods for VEGF/PDGF family of growth factors
WO2005119244A1 (en) * 2004-06-03 2005-12-15 Phylogica Limited Peptide modulators of cellular phenotype and bi-nucleic acid fragment library
PL1974020T3 (en) * 2005-12-16 2011-11-30 Ribovax Biotechnologies Sa Methods for obtaining immortalized antibody secreting cells
ES2683846T3 (en) 2006-01-20 2018-09-28 Cell Signaling Technology, Inc. ROS mutant and translocation kinase in human non-small cell lung carcinoma
US20120208824A1 (en) 2006-01-20 2012-08-16 Cell Signaling Technology, Inc. ROS Kinase in Lung Cancer
US8575070B2 (en) * 2006-02-20 2013-11-05 Phylogica Limited Methods of constructing and screening libraries of peptide structures
ES2561406T3 (en) 2006-04-14 2016-02-26 Cell Signaling Technology, Inc. ALK gene and kinase mutant defects in solid human tumors
AU2007299562A1 (en) * 2006-09-19 2008-03-27 Phylogica Limited Neuroprotective peptide inhibitors of AP-1 signaling and uses therefor
EP2170932A4 (en) * 2007-06-20 2012-10-10 Phylogica Ltd Compositions and uses thereof for the treatment of acute respiratory distress syndrome (ards) and clinical disorders associated with therewith
EP3753947A1 (en) 2007-09-14 2020-12-23 Adimab, LLC Rationally designed, synthetic antibody libraries and uses therefor
US8877688B2 (en) 2007-09-14 2014-11-04 Adimab, Llc Rationally designed, synthetic antibody libraries and uses therefor
EP3072963B1 (en) 2007-10-18 2020-04-01 Cell Signaling Technology, Inc. Translocation and mutant ros kinase in human non-small cell lung carcinoma
US9873957B2 (en) 2008-03-13 2018-01-23 Dyax Corp. Libraries of genetic packages comprising novel HC CDR3 designs
CA2968164C (en) 2008-04-24 2019-08-20 Dyax Corp. Libraries of genetic packages comprising novel hc cdr1, cdr2, and cdr3 and novel lc cdr1, cdr2, and cdr3 designs
PL2881402T3 (en) 2009-02-12 2017-10-31 Cell Signaling Technology Inc Mutant ROS expression in human liver cancer
AU2010291902A1 (en) * 2009-09-14 2012-04-05 Dyax Corp. Libraries of genetic packages comprising novel HC CDR3 designs
WO2011084605A1 (en) * 2009-12-16 2011-07-14 The Trustees Of The University Of Pennsylvania Anti-prostate cancer antibodies and methods of detection and treatment of prostate cancer using the same
MX360336B (en) 2010-07-16 2018-10-30 Adimab Llc Star Antibody libraries.
US20120101108A1 (en) 2010-08-06 2012-04-26 Cell Signaling Technology, Inc. Anaplastic Lymphoma Kinase In Kidney Cancer
EP3103810A3 (en) 2011-04-21 2017-03-08 Garvan Institute of Medical Research Modified variable domain molecules and methods for producing and using them
ES2655842T3 (en) 2012-04-18 2018-02-21 Cell Signaling Technology, Inc. EGFR and ROS1 in cancer
WO2015184321A2 (en) * 2014-05-29 2015-12-03 Siemens Healthcare Diagnostics Inc. Rare molecule detection
NZ760841A (en) 2017-07-11 2024-02-23 Compass Therapeutics Llc Agonist antibodies that bind human cd137 and uses thereof
US11718679B2 (en) 2017-10-31 2023-08-08 Compass Therapeutics Llc CD137 antibodies and PD-1 antagonists and uses thereof
EP3713961A2 (en) 2017-11-20 2020-09-30 Compass Therapeutics LLC Cd137 antibodies and tumor antigen-targeting antibodies and uses thereof
AU2019379576A1 (en) 2018-11-13 2021-06-03 Compass Therapeutics Llc Multispecific binding constructs against checkpoint molecules and uses thereof

Citations (2)

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Publication number Priority date Publication date Assignee Title
WO1990014430A1 (en) * 1989-05-16 1990-11-29 Scripps Clinic And Research Foundation A new method for tapping the immunological repertoire
WO1991010737A1 (en) * 1990-01-11 1991-07-25 Molecular Affinities Corporation Production of antibodies using gene libraries

Family Cites Families (3)

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JP2919890B2 (en) 1988-11-11 1999-07-19 メディカル リサーチ カウンスル Single domain ligand, receptor consisting of the ligand, method for producing the same, and use of the ligand and the receptor
CA2016841C (en) 1989-05-16 1999-09-21 William D. Huse A method for producing polymers having a preselected activity
DK0440147T3 (en) 1990-02-01 2005-01-17 Dade Behring Marburg Gmbh Preparation and use of human antibody gene banks ("human antibody libraries")

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990014430A1 (en) * 1989-05-16 1990-11-29 Scripps Clinic And Research Foundation A new method for tapping the immunological repertoire
WO1991010737A1 (en) * 1990-01-11 1991-07-25 Molecular Affinities Corporation Production of antibodies using gene libraries

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
WINTER G., MILSTEIN C.: "MAN-MADE ANTIBODIES.", NATURE, NATURE PUBLISHING GROUP, UNITED KINGDOM, vol. 349., 24 January 1991 (1991-01-24), United Kingdom, pages 293 - 299., XP000572614, ISSN: 0028-0836, DOI: 10.1038/349293a0 *

Also Published As

Publication number Publication date
ATE277179T1 (en) 2004-10-15
EP1566442A3 (en) 2006-06-07
ATE449853T1 (en) 2009-12-15
PT96625B (en) 1998-07-31
AU633682B2 (en) 1993-02-04
IE910335A1 (en) 1991-08-14
AU7011391A (en) 1991-08-08
CA2035381A1 (en) 1991-08-02
CA2035381C (en) 2004-11-09
EP0440147B1 (en) 2004-09-22
ES2225816T3 (en) 2005-03-16
EP1566442B1 (en) 2009-11-25
DK0440147T3 (en) 2005-01-17
EP1566442A2 (en) 2005-08-24
DE59109264D1 (en) 2004-10-28
US6319690B1 (en) 2001-11-20
ES2336444T3 (en) 2010-04-13
JPH04211394A (en) 1992-08-03
KR910021475A (en) 1991-12-20
ES2225816T5 (en) 2014-08-21
PT96625A (en) 1991-11-29
EP0440147A2 (en) 1991-08-07
KR100186823B1 (en) 1999-04-01
JP3514778B2 (en) 2004-03-31
DE59109273D1 (en) 2010-01-07
EP0440147B2 (en) 2014-05-14

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